Autism spectrum disorder (ASD) is characterized by social impairments and affects 1 in 68 US children, but remains poorly understood. Few biomarkers of ASD have been identified, hindering the understanding of its basic biology; nor are there any medications that treat the social deficits of ASD. Progress has been impeded by: 1) the difficulty of obtaining relevant tissue samples from patients and matched controls, and 2) in mouse models, the discordance between complex human behavior and laboratory-based mouse behavior, even with shared genetic etiologies. These two limitations underscore the tremendous value in developing an animal model of social deficits with more reliable behavioral and biological correlates to the human disease. Rhesus monkeys are an ideal model organism. Like humans, they are highly social, and both species display stable and pronounced individual differences in social functioning. At the behavioral extremes, low-social compared to high-social male rhesus monkeys initiate fewer affiliative interactions and display more inappropriate social behavior, suggesting both lower social motivation and poorer social skills. Naturally occurring low-social behavior in male rhesus monkeys therefore presents an exceptional opportunity to study the biology of social impairments. This research leverages a novel statistical classification model which predicts, from infant behavior, subjects that are subsequently found to be low-social or high-social. On the basis of promising pilot data, we will collect quantitative social behavior data in a larger validation cohort of 1-5 year old male monkeys to confirm the discriminant power of this statistical model to be used as a robust high-throughput screening tool to rapidly identify social extremes in a large population. We will also test whether: our candidate biomarkers of social functioning (e.g., oxytocin and arginine-vasopressin; kinase signaling) correctly classify monkeys as low- social vs. high-social; the degree of biomarker dysregulation co-varies with the degree of social deficits; and cerebrospinal fluid and blood measures are equally informative. Because exclusion of females may impede identification of important disease mechanisms, we will also test, for the first time, whether our statistical classification model can be used to identify social extremes in female monkeys, and whether the same or different biomarkers predict social deficits in low-social females. Finally, we will create the first primate social behavior test battery to better characterize the impairments of low-social monkeys with direct relevance to core autism symptoms (e.g., deficits in joint attention, face recognition, social learning, social competence, theory of mind, peer preferences). Creation of this battery will also allow us to test which biomarker measurements most robustly predict low-social monkey test performance to identify the most promising targets for therapeutic intervention. We are optimistic that further development of this model will accelerate the discovery of autism biomarkers and novel druggable targets, provide non-behavioral biometrics for treatment response, and streamline the development of the first effective autism therapeutics.